tbuckley/cabot-search huggingface dataset:
ORIENT-32: Updated characterization of response to sintilimab plus bevacizumab biosimilar (IBI305) vs sorafenib for unresectable hepatocellular carcinoma.
Authors: Zhenggang Ren, Jianming Xu, Yuxian Bai, Aibing Xu, Shundong Cang, Chengyou Du, Baorui Liu, Qiu Li, Yinying Lu, Yajin Chen, Guoliang Shao, Yabing Guo, Zhendong Chen, Jia Fan
Journal: Journal of Clinical Oncology (2023)

570 Background: ORIENT-32 trial (NCT03794440) assessed sintilimab (anti-PD-1 antibody) plus a bevacizumab biosimilar (anti-VEGF antibody) versus sorafenib (Sor) as first-line treatment for unresectable HCC and demonstrated a significant improvement in both overall survival and progression-free survival. Here we report the updated results of objective response rate (ORR), time to response (TTR), duration of response (DoR) and depth of response (DpR). Methods: 571 eligible patients (pts) with unresectable HCC were enrolled and randomized (2:1) to receive sintilimab (200 mg IV Q3W) plus IBI305 (15 mg/kg IV Q3W) or Sor (400 mg orally, BID) until disease progression or unacceptable toxicity. Tumors were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)and HCC-modified RECIST (mRECIST). ORR, TTR, DoR, and DpR were analyzed. The DpR was defined as the minimum percentage of (1) sum of longest diameter (SLD) change and (2) longest diameter (LD) change described as mean (standard deviation, SD). Results: At the data cutoff on Dec 30th, 2021, the median follow-up time was 26.7 months. The ORR in sintilimab plus IBI305 and Sor group was 21.0% (77/367) vs 4.7 (8/169) per RECIST 1.1 and 25.1% (92/367) vs 7.7% (13/169) per mRECIST. The median TTR in sintilimab plus IBI305 group was 2.8 (2.4–3.3) months per RECIST 1.1 and 2.6 (1.6–2.9) months per mRECIST. The median DoR in sintilimab plus IBI305gourp was 20.3 (12.3-NE) months per RECIST 1.1. The minimum percentage of SLD change was larger in the sintilimab plus IBI305 arm than in the Sor arm: (−13.4% (35.8) vs 3.2%(26.5) per RECIST 1.1). Similarly, the LD change in the largest liver lesion also favored sintilimab plus IBI305 arm (−27.6% (31.6) vs −11.5% (20.9)), including larger tumors (≥7 cm; −21.2% (30.4) vs −9.9% (23.7)) all per RECIST 1.1. Conclusions: Sintilimab plus IBI305 showed a significant improvement in ORR, TTR, DOR and DpR vs Sor in unresectable HCC. Clinical trial information: NCT03794440 .
Clinical outcomes and healthcare utilization among young adults with colon cancer on Medicaid vs private insurance.
Authors: Vaishali Deenadayalan, Vinod Solipuram, Harry Guillermo Sequeira Gross, Shweta Gupta
Journal: Journal of Clinical Oncology (2023)

22 Background: The incidence of colon cancer in young adults has been increasing. The role of insurance on the outcomes of young adults diagnosed with colon cancer is unclear. In this study we sought to study the impact of Private insurance vs Medicaid on the outcomes of colon cancer in young adults (&lt;50 years). Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016-2019 was queried to identify young adult patients (Age &lt;50 years) admitted for colon cancer using the ICD-10 (International Classification of Diseases) codes. Study population was stratified based on the insurance (private vs Medicaid). Primary outcomes included mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included prevalence of pulmonary embolism (PE), ICU admission, acute kidney injury (AKI), acute respiratory failure (ARF), blood transfusion, and sepsis. Statistics were performed using multivariate linear and logistic regression using STATA v17. Results: 59,065 young adult admissions were identified with a principal diagnosis of colon cancer between 2016-2019. Among them 36,765 (62.2%) were on private insurance while 13,480 (22.8%) were on Medicaid. Medicaid patients were significantly younger, female, Black and Hispanic with a higher Charlson comorbidity index (p&lt;0.05). Of the 870 (1.5%) patients that died during the admission, 46.5% (N= 405) had private insurance whereas 26.4% (N= 230) had Medicaid. There was no significant difference in the odds of mortality between private insurance and Medicaid (adjusted OR 1.07, 95% CI 0.69-1.67; p=0.77). The LOS was increased by 1.5 days for Medicaid patients compared to private insurance (95% CI 1.15-1.90; p&lt;0.001). There was no significant difference in total hospitalization charges among both groups. Medicaid patients had higher odds of sepsis (OR 1.5, 95% CI 1.09-1.94; p=0.012), requiring blood transfusion (OR 1.6, 95% CI 1.32-1.83; p&lt;0.000) and less likely to undergo colectomy (OR 0.61, 95% CI 0.55-0.67; p&lt;0.000). There were no significant differences in ICU admission, AKI and ARF. Conclusions: Compared to private insurance, Medicaid patients had similar healthcare outcomes and hospital charges despite a longer LOS. In an era where the country explores options for healthcare reform including single payor system, our study provides insight into similar effectiveness of Medicaid in caring for young colon cancer patients compared to Private Insurance despite higher comorbidities in Medicaid patients.
A multiplex DNA methylation assay for noninvasive early detection of gastric cancer.
Authors: Weimei Ruan, Xiaotian Lei, Weihong Sha, Bin Li, Hong Wang, Yuying Xia, Junran Shen, Lingchen Kong, Juan Ma, Zhiwei Chen, Marina Bibikova, Chunhui Cui, Jian-Bing Fan
Journal: Journal of Clinical Oncology (2023)

300 Background: Gastric cancer (GC) is the fifth leading cancer that ranked fourth in cancer mortality worldwide. Early screening and detection can significantly improve patients’ prognosis and survival. Although in standard GC diagnosis, gastroscopy provides sufficient diagnostic power for identifying GC in early stages, the invasive and costly procedure is not suitable for screening and has low compliance in countries with high GC incidence and large populations. Furthermore, the serum-based GC related biomarkers and non-invasive tests (serum pepsinogen I and II, gastrin-17, and anti-Helicobacter pylori IgG antibody tests) showed insufficient evidence as cost-effective GC screening approaches. A non-invasive DNA methylation assay with high sensitivity was aimed to develop and validate as a potential alternative for GC early detection. Methods: A multiplex quantitative PCR (qPCR) assay for detecting GC-specific DNA methylation markers in plasma was developed, in which the markers were further optimized from a reported seven-marker panel based on a pilot case-control study with 63 GC and 130 non-GC samples. The GC detection model of the assay was developed and locked down in the first cohort consisting of 54 GC and 79 non-GC samples. The second validation cohort with 117 GC and 309 non-GC samples was used to evaluate the assay performance. All plasma samples used in the two cohorts were prospectively collected from patients diagnosed with GC or other gastrointestinal diseases or from healthy donors. Results: The multiplex DNA methylation assay showed an overall sensitivity and specificity of 80% (95% CI: 77–83%) and 65% (95% CI: 63–66%) in the model development cohort, respectively, with a sensitivity of 80% (95% CI: 65–95%, n=10) in the detection of stage I GC. The assay revealed similar performance characteristics in the validation cohort, with an overall sensitivity of 82% (95% CI: 80–83%), a specificity of 69% (95% CI: 68–69%), and a sensitivity of 78% (95% CI: 74–82%, n=41) for the stage I GC detection. The DNA methylation assay outperformed the reported serum-based GC related biomarkers and non-invasive tests (sensitivity of 69.6-70.7% and specificity of 66.8-67.8%) with higher sensitivity, particularly in the stage I GC with a comparable specificity. Conclusions: The multiplex DNA methylation assay provides a potential cost-effective tool that features high sensitivity for GC early detection.
Efficacy and safety of TACE combined with anlotinib compared with TACE alone among patients with intermediate or advanced hepatocellular carcinoma (HCC): A randomized, controlled, phase II clinical study.
Authors: Hui Zeng, Guoliang Shao
Journal: Journal of Clinical Oncology (2023)

581 Background: Anlotinib hydrochloride is an oral multi targeted tyrosine kinase inhibitor, mainly targeting VEGFR1-3, FGFR 1-4 and PDGFR α/β. Transcatheter arterial chemoembolization (TACE) is the preferred choice for the treatment of intermediate or advanced HCC. Previous studies have proved that antiangiogenic drugs combined with TACE have synergistic effects. The purpose of this study was to explore the efficacy and safety of TACE combined with anlotinib in the treatment of intermediate or advanced liver cancer compared with TACE alone. Methods: This single-center, randomized controlled, phase II study involved 38 HCC patients with BCLC staging B or C and ECOG PS ≤ 1. Enrolled pts were treated with TACE plus anlotinib (12mg, qd, d1-d14, q3w) and TACE alone until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS), the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Both PFS and tumor response were assessed by investigator per RECIST v1.1. Results: At the cutoff date of April 2022, 18 pts received TACE combined anlotinib and 20 pts received TACE alone. The median PFS was 11.04 months (95%CI, 7.17-14.92) in combination group and 6.87 months (95%CI, 5.58-8.16) in TACE group (HR 0.46, 95% CI 0.23 to 0.92, P=0.022). The median OS has not been reached yet. ORR was 27.8% (95%CI, 9.7%-53.5%) and 30% (95%CI, 11.9%-54.3%) and DCR was 94.4% (95%CI 72.7%-99.9%) and 100% (95%CI 83.2%-100%), respectively, with no statistical difference.The median times of TACE are 2 and 3 respectively.The treatment-related adverse events (TRAEs) of any grade occurred in 15 patients (83.3%) and 19 patients (95%). The most common TRAEs were HFSR (61.1%), hypertension (27.8%), thrombocytopenia (11.1%) in combination group and vomiting (35%), upper abdominal liver pain (35%), upper abdomen pain (30%), low fever (10%), fatigue (10%) in TACE group.Grade ≥ 3 TRAEs occurred in 2 pts (11.1%) in combination group and 1pts (5%) in TACE group. Conclusions: Anlotinib combined with TACE is a safe and effective regimen in the treatment ofpatients with intermediate or advanced-stage hepatocellular carcinoma (HCC). This study still needs longer follow-up to evaluate its efficacy more comprehensively. Clinical trial information: NCT04066543 .
An active trend of immunotherapy combination regimen as second-line therapy for advanced biliary tract cancer: A multicenter retrospective study.
Authors: Jieer Ying, Haimin Weng, Qi Xu, Jingjing Li, Qing Wei, Pengfei Zeng, Yuemiao Chen
Journal: Journal of Clinical Oncology (2023)

520 Background: FOLFOX as second-line therapy remains the standard of care in patients with biliary tract cancer (BTC), but its efficacy is suboptimal. Currently, cytotoxic chemotherapy, targeted therapy, and immunotherapy alone or in combination are being tested in patients with pretreated advanced BTC for in clinical trials. This study aimed to evaluate and compare the anticancer of distinct treatment regimen in patients with advanced BTCs who progress after first-line chemotherapy. Methods: Patients diagnosed BTC who received second-line therapy were retrospectively identified at 3 sites across the Zhejiang province between January 1, 2018, and June 31, 2022. Clinicopathological information and therapeutic outcome, including subtype of BTC, response per RECIST v1.1, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated. Results: A total of 98 patients with BTCs were reviewed and recruited eventually: the chemotherapy group (cohort A, n=30), the chemotherapy plus ICIs group (cohort B, n=25), the TKIs group (cohort C, n=17), and the TKIs plus ICIs group (cohort D, n=26). The median PFS and OS were 2.4 months (95%CI: 1.6–3.2) and 7.0 months (95% CI: 6.4–7.5) for cohort A, 3.9 months (95%CI: 2.8–5.0) and 10.7 months (95% CI: 6.9–14.5) for cohort B, 1.6 months (95%CI: 0.8–2.4) and 7.1 months (95% CI: 0.7–13.5) for cohort C, and 4.7 months (95%CI: 3.1–6.2) and 10.1 months (95% CI: 4.1–16.1) for cohort D, respectively. In the cohort A, B, C, and D, confirmed ORRs were 10%, 20%, 11.8% and 19.2%, separately, and DCRs were 46.7%, 68%, 43.8% and 76.9%, respectively. The efficacy of ICIs plus TKIs was optimal in terms of tumor response and associated with prolong PFS. Six patients (20%), nine patients (36%), five patients (29.4%), and elven patients (42.3%) were experienced ≥ grade 3 treatment-related AEs in cohort A, B, C, and D, respectively. Conclusions: Immunotherapy combination strategy beyond first-line systemic chemotherapy plays a positive role in advanced BTCs. Both TKIs plus ICIs and chemotherapy plus ICIs could be considered as candidates to second-line trails and turn into a competitive second-line treatment regimen for advanced BTCs in clinical practice.
Efficacy of sequential perioperative FOLFIRNOX plus gemcitabine nab-paclitaxel for resected pancreatic and periampullary cancers.
Authors: Putao Cen, Kok Hoe Chan, Curtis Jackson Wray, Nirav Thosani, John Bynon, Julie Haewon Rowe
Journal: Journal of Clinical Oncology (2023)

724 Background: Perioperative chemotherapy with single regimen either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (Gem/NabP) is the current standard of care for pancreatic and periampullary cancers (PC) with overall survival (OS) of 2-3 years without pre-selected CA19-9 level. Sequential chemotherapy with FFX plus Gem/NabP has recently been investigated in metastatic PC and shown to improve OS. We investigated the outcome of patients who received sequential perioperative chemotherapy FFX plus Gem/NabP. Methods: Patients treated with curative intent surgery for PC who received perioperative sequential chemotherapy FFX plus Gem/NabP (each regimen was given at least two months) were identified. OS and recurrence-free survival (RFS) were calculated from the date of initial treatment (neoadjuvant chemotherapy or resection) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 29 patients were identified: 24 (83%) patients had pancreatic cancer, 5 (17%) patients had periampullary cancer; 16 (55%) patients received neoadjuvant chemotherapy FFX plus Gem/NabP; 13 (45%) patients underwent upfront surgery and received adjuvant FFX plus Gem/NabP chemotherapy; 22 (76%) patients had resectable disease, the rest 7 (24%) patients had borderline or unresectable disease were all in the neoadjuvant cohort; node positivity was higher in the adjuvant cohort (n=8, 62%) than in the neoadjuvant cohort (n=8, 50%); 5 (17%) patients were found to have homologous recombination deficiency (HRD: BRCA2, CHEK, BARD, ATM) and received PARP inhibitors as part of the perioperative therapy combination. 10 (34%) patients had CA19-9 ≥ 500. Median age was 65 years (range, 45-79 years), 20 (69%) were male. During the study period, 4 (14%) patients died, and 6 (21%) patients had disease recurrence. Median RFS and OS were not reached with a median follow-up of 28 months (range, 10.9–119 months). The longest RFS was 10 years. The 2-years RFS and OS for the entire cohort was 76.7% and 88.8%, respectively. There was no statistical difference in RFS (log rank HR 1.72, 95% CI 0.23-13.15) or OS (log rank HR 0.99, 95% CI 0.20-4.93) for patients in the neoadjuvant cohort versus adjuvant cohort. Conclusions: Sequential perioperative chemotherapy combined FFX plus Gem/NabP for resected PC is effective and potentially prolongs survival, compared to historical controls who received single regimen.[Table: see text]
Randomized, global, phase 3 study of tislelizumab (TIS) + chemotherapy (chemo) versus placebo (PBO) + chemo as first-line (1L) treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Non-Asia subgroup.
Authors: Eric Raymond, Richard Hubner, Evgeny Gotovkin, Lucjan Wyrwicz, Eric Van Cutsem, Paula Jimenez-Fonseca, Roberto Pazo-Cid, Jianming Xu, Ken Kato, Aiyang Tao, Lei Wang, Yanyan Peng, Liyun Li, Harry H. Yoon
Journal: Journal of Clinical Oncology (2023)

340 Background: TIS, an anti-programmed cell death protein 1 (PD-1) antibody, + chemo as 1L therapy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) vs PBO + chemo in patients with advanced or metastatic ESCC (hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.54, 0.80]; P&lt; 0.0001), with a manageable safety profile, at interim analysis of the phase 3, double-blind RATIONALE-306 study (NCT03783442). Here, we report data from the non-Asia subgroup (Europe, Northern America, and Oceania). Methods: Adults with advanced or metastatic ESCC, with no prior systemic treatment for advanced disease were randomized 1:1, (stratified by region, prior definitive therapy, and investigator [INV]-chosen chemo) to receive TIS 200 mg intravenously (IV) once every 3 weeks (Q3W) (Arm A) or PBO IV Q3W (Arm B), with platinum + fluoropyrimidine, or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) by INV per RECIST v1.1; OS in the programmed death-ligand 1 score ≥10%; and safety. Results: Of 649 randomized patients, 163 (25.1%) were from the non-Asia subgroup (Arm A, n = 83; Arm B, n = 80). At data cutoff (Feb 28, 2022), the median study follow-up time in the non-Asia subgroup was 16.0 months (mo) in Arm A vs 8.4 mo in Arm B. OS (median 16.3 vs 9.0 mo; unstratified HR 0.66 [95% CI 0.45, 0.96]) and PFS (median 7.7 vs 5.5 mo; unstratified HR 0.59 [95% CI 0.41, 0.83]) were improved in Arm A vs Arm B, respectively. Arm A had higher ORR (61.4% vs 41.3%, odds ratio 2.27 [95% CI 1.21, 4.25]) and longer median DoR (7.1 mo [95% CI 5.6, 9.6] vs 5.7 mo [95% CI 3.8, 8.3]) than Arm B. More patients in Arm A vs Arm B experienced ≥1 treatment-related adverse event (TRAE; 94.0% vs 88.5%), serious TRAEs (25.3% vs 17.9%), and discontinuation due to treatment-emergent AEs (42.2% vs 35.9%, respectively). Similar proportions of patients in Arm A vs Arm B had ≥grade 3 TRAEs (56.6% vs 52.6%), and TRAEs leading to death (1.2% vs 1.3%), respectively. Conclusions: In the non-Asia subgroup, 1L TIS + chemo showed a clinically meaningful improvement in OS vs PBO + chemo in patients with advanced or metastatic ESCC, with a manageable safety profile, consistent with published results in the overall population. Clinical trial information: NCT03783442 .
Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image-guided intensity modulated radiation therapy in locally advanced rectal cancers.
Authors: Raunaq Puri, Madhup Rastogi, Ajeet Kumar Gandhi, Rohini Khurana, Rahat Hadi, Shanyanu Sapru, Anoop Srivastava, Avinav Bharati, Surendra Prasad Mishra
Journal: Journal of Clinical Oncology (2023)

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m 2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]
Clinical efficacy and biomarker analysis of pucotenlimab (HX008) in patients with previously treated advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A single-arm, multicenter, phase 2 study.
Authors: Bo Zhang, Yan Song, Suxia Luo, Xianli Yin, Enxiao Li, Hui Wang, Yifu He, Zhihui Liu, Qingxia Fan, Xinjun Liang, Yongqian Shu, Yunpeng Liu, Nong Xu, Shu Zhang, Zhixiang Zhuang, Jingdong Zhang, Xiaoge Kou, Fen Wang, Xiaodong Zhu, Jing Huang
Journal: Journal of Clinical Oncology (2023)

799 Background: Pucotenlimab is a humanized IgG4 anti-PD-1 monoclonal antibody with an engineered Fc domain. We aim to assess the efficacy and safety of pucotenlimab, and potential predictive biomarkers of response in patients with previously treated advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had locally advanced or metastatic, centrally confirmed MSI-H or dMMR solid tumors treated with at least one prior systemic therapy. Patients received pucotenlimab 200mg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed by the independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Besides, patients’ PD-L1 expression, blood neutrophil to lymphocyte ratio (NLR), germline HLA-I genotyping, loss of heterozygosity (LOH) of HLA-I genes, tumor mutational burden (TMB), and genetic alterations in the tumor revealed by next-generation sequencing were investigated to identify potential predictors of efficacy. Results: 100 patients with MSI-H or dMMR solid tumors were enrolled. Colorectal cancer (n=71) and gastric cancer (n=10) were the most common cancer types. The median follow-up duration was 22.5 months (range: 0.3-37.4) at data cutoff (December 4, 2021). The ORR was 49.0% (95% CI 38.86%-59.20%), and the 12-month progression-free survival (PFS) rate was 56.1% (95% CI 45.63%-65.24%) based on IRC’s assessment. Both the median PFS and median duration of response were not reached. Pucotenlimab was well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 18 patients, most commonly anemia, leukocytopenia, and hypertension. For the biomarker analysis, patients with NLR &lt;4 at the second treatment cycle, TMB≥32.5 muts/Mb (the lower 35th TMB-percentile), or mutations in the KMT2D gene showed significantly higher ORR. Conclusions: Pucotenlimab demonstrated durable antitumor activity and manageable safety for previously treated patients with advanced MSI-H/dMMR solid tumors. KMT2D gene mutation, along with NLR and TMB, warrants further investigation as predictive biomarkers. Clinical trial information: NCT03704246 .